Cytolytic T-lymphocytes (also called "cytotoxic T-lymphocytes," and typically abbreviated "CTLs") are a class of T-cells that adhere to and lyse target cells. Most CTLs are restricted in their targeting activity by recognizing, on the surface of a target cell, a Class I major histocompatibility molecule (Class I MHC) bearing an associated antigen. Interaction between the CTL and its target is believed to be mediated by adhesion of a T-cell receptor (TCR) and an associated complex of proteins known as "CD3" (together referred to as the "TCR:CD3" complex), with an MHC-antigen complex on the target cell. CTLs, which interact with Class I MHC molecules, frequently possess another accessory protein called "CD8." CD8 is thought to be a CTL surface glycoprotein that facilitates the interaction between the TCR:CD3 complex and the MHC:antigen complex. CD8 binds to a region on the Class I MHC molecule different from the TCR:CD3 binding site and enhances adhesion. The CD8 molecule is also involved in mediating signal transduction and otherwise modulating the functional responses that accompany binding of the CTL to its target.
One of the primary functions of the CTL system is to destroy cells which are producing foreign antigens, such as cells infected with a virus. However, CTLs are also involved in the destruction of foreign cells that were purposely introduced into the body as grafts or transplants from allogeneic hosts. This process, known as "allograft rejection," involves the interaction of host CTLs with foreign MHC molecules. The most commonly used approach to preventing allograft rejection is to suppress the immune system in the recipient; typically by using immunosuppressive drugs. However, use of these drugs can cause severe side effects including nephrotoxicity, hypertension, bone loss and lymphoma. Another approach has been the use of antibodies to human T-cells, such as OKT3 and OKT4. However, problems have been encountered with that approach because humans mount antibody responses against the proteins, rendering them ineffective.
There remains a substantial need for ways to control the cytolytic system in a host by selectively modulating T-cell activities. Major improvements in tissue transplantation could be obtained with the development of more specific, less toxic therapies to prevent allograft rejection.